Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT01413750
Other study ID # NCI-2010-02203
Secondary ID NCI-2010-02203PH
Status Terminated
Phase Phase 1/Phase 2
First received August 5, 2011
Last updated July 22, 2015
Start date November 2010
Est. completion date April 2013

Study information

Verified date September 2013
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving carboplatin and paclitaxel together is more effective with or without vorinostat in treating non-small cell lung cancer.


Description:

PRIMARY OBJECTIVES:

I. To compare progression-free survival associated with the combination of carboplatin, paclitaxel and vorinostat versus carboplatin, paclitaxel and placebo for patients with previously untreated, advanced NSCLC.

SECONDARY OBJECTIVES:

I. To determine the response rate, time to treatment failure, and overall survival for the two regimens.

II. To assess the safety profile of the regimen of vorinostat, carboplatin and paclitaxel for patients with advanced NSCLC.

III. To understand the mechanistic aspects of drug effect by conducting correlative science studies on peripheral blood and archived tumor tissue.

An initial safety run-in study is planned (phase I) before starting the phase II randomized study as described below. Doses of Vorinostat to be tested during the safety run-in portion are: Dose Level -1 500 mg QD, Dose Level 1 600 mg QD, Dose Level 2 800 mg QD. Patients will not be randomized during the safety lead-in period, and no patients treated during the lead-in will be considered in the primary evaluation of each arm in any comparison. Once the safety run-in portion is completed, all patients will randomized to receive either placebo or vorinostat at a fixed dose determined during the run-in portion.

Phase II Portion of Study:

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel IV over 3 hours, and carboplatin IV over 30 minutes on day 0. Patients also receive vorinostat orally (PO) once daily on days -2 to 2.

ARM II: Patients receive paclitaxel and carboplatin as in arm I. Patients also receive placebo PO once daily on days -2 to 2.

In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, quarterly for 1 year, and then twice a year thereafter.


Recruitment information / eligibility

Status Terminated
Enrollment 23
Est. completion date April 2013
Est. primary completion date April 2013
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

- Patients must have histologically confirmed non-small cell lung cancer

- No prior chemotherapy for advanced or metastatic disease

- ECOG performance status 0 or 1

- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan

- Life expectancy of greater than 12 weeks

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) =< 2.5 x institutional upper limit of normal

- Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy in a metastatic setting

- Patients may not be receiving any other investigational agents

- Patients with untreated brain metastases should be excluded from this clinical trial; however, patients who have stable brain disease (should be off corticosteroids) at least 3 weeks after completion of appropriate therapy are eligible

- Patients who have received any prior HDAC inhibitor (except valproic acid for seizure control provided that the valproic acid has been stopped at least 30 days before beginning therapy on this protocol) are excluded from this study

- Peripheral neuropathy of severity greater than grade 1

- Known history of allergic reactions to paclitaxel

- Prior therapy with paclitaxel

- Inability to take oral medications on a continuous basis; patients unable to swallow the vorinostat capsules whole are ineligible (the capsules cannot be crushed or broken)

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with vorinostat; women of childbearing potential must use an appropriate double barrier method of birth control (such as female use of a diaphragm, intrauterine device [IUD], sponge and spermicide, in addition to the male use of a condom) or a prescribed birth control implant or practice abstinence; both double barrier contraception and implants must be used for at least one week prior to the start of the research study and continue for at least two weeks following the last study visit; please note that birth control pills should not be used while on this study as they may have a negative interaction with the experimental drug in this study

- HIV-positive patients receiving combination antiretroviral therapy are ineligible

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
Paclitaxel
Given IV
Carboplatin
Given IV
Vorinostat
Given PO
Other:
Placebo
Given PO
Laboratory Biomarker Analysis
Correlative studies

Locations

Country Name City State
United States Emory University/Winship Cancer Institute Atlanta Georgia
United States University of North Carolina Chapel Hill North Carolina
United States City of Hope Comprehensive Cancer Center Duarte California
United States City of Hope Medical Center Duarte California
United States Penn State Milton S Hershey Medical Center Hershey Pennsylvania
United States USC / Norris Comprehensive Cancer Center Los Angeles California
United States Vanderbilt-Ingram Cancer Center Nashville Tennessee
United States Illinois CancerCare-Peoria Peoria Illinois
United States University of Pittsburgh Pittsburgh Pennsylvania
United States University of Pittsburgh Cancer Institute Pittsburgh Pennsylvania
United States Virginia Commonwealth University/Massey Cancer Center Richmond Virginia
United States University of California Davis Comprehensive Cancer Center Sacramento California
United States Saint John's Mercy Medical Center Saint Louis Missouri
United States Southern Illinois University School of Medicine - Obstetrics and Oncology Springfield Illinois
United States Moffitt Cancer Center Tampa Florida

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Progression-free Survival (PFS) Estimated using the product-limit method of Kaplan and Meier.
PFS defined as time from randomization to progression or death due to any cause.
Progression defined as Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 1 year No
Secondary Dose Limiting Toxicity (DLT) (Phase I) DLT is defined as any grade III or higher non-hematological toxicity except nausea, vomiting or alopecia. Nausea or vomiting (> grade 2) that last longer than 48 hours despite maximal medical therapy. Absolute neutrophil count < 1000/uL lasting longer than 7 days. Grade 4 thrombocytopenia (platelet < 25,000/uL). Grade 3 or 4 neutropenia associated with sepsis or fever > 38 C. Delay in starting cycle 2 by more than 2 weeks due to toxicity.Abnormal non-hematological laboratory criteria (Grade 3 or higher) will be considered a DLT, if clinically significant and drug-related. If baseline value is elevated prior to drug therapy, an increase will not be considered a DLT unless there is an elevation by more than 2 grades, and it is of clinical significance. Dose escalation schedule for vorinostat: 600 mg QD; 800 mg QD. 4 weeks from start of treatment, up to 1 year Yes
Secondary Maximum Tolerated Dose (MTD) (Phase I) The highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. The MTD is one dose level below the lowest dose in which 33% or more of the patients experience a DLT. The MTD is based on the first cycle of therapy. The recommended Phase II dose is generally the MTD, although secondary considerations of toxicity and dose reductions on subsequent cycles and other secondary considerations may result in the recommended Phase II dose being below the MTD. 4 weeks from start of treatment, up to 1 year Yes
See also
  Status Clinical Trial Phase
Completed NCT01664754 - Exemestane, Pemetrexed Disodium, and Carboplatin in Treating Post-Menopausal Women With Stage IV Non-Small Cell Lung Cancer Phase 1
Completed NCT02451930 - A Study of the Combination of Necitumumab (LY3012211) and Pembrolizumab (MK3475) in Participants With NSCLC Phase 1
Withdrawn NCT02106559 - Photodynamic Therapy During Surgery in Treating Patients With Pleural Malignancy N/A
Completed NCT02364609 - Pembrolizumab and Afatinib in Patients With Non-small Cell Lung Cancer With Resistance to Erlotinib Phase 1
Terminated NCT02495896 - Recombinant EphB4-HSA Fusion Protein With Standard Chemotherapy Regimens in Treating Patients With Advanced or Metastatic Solid Tumors Phase 1
Completed NCT01935336 - Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers Phase 2
Withdrawn NCT01971489 - Buparlisib, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Advanced Solid Tumors Phase 1
Completed NCT01839955 - Erlotinib Hydrochloride and Quinacrine Dihydrochloride in Stage IIIB-IV Non-Small Cell Lung Cancer Phase 1
Terminated NCT01193868 - RO4929097 in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Recently Completed Treatment With Front-Line Chemotherapy Phase 2
Completed NCT00986674 - Carboplatin and Paclitaxel Combined With Cetuximab and/or IMC-A12 in Patients With Advanced Non-Small Cell Lung Cancer Phase 2
Completed NCT00963807 - Trial Comparing the Use of FLT PET to Standard CT to Assess Treatment Response of Neoadjuvant Docetaxel and Cisplatin in Stage IB-IIIA Resectable NSCLC Phase 2
Completed NCT00087412 - S0341: Erlotinib in Treating Patients With Advanced Primary Non-Small Cell Lung Cancer Phase 2
Completed NCT00085280 - Erlotinib in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer N/A
Completed NCT00052338 - Bortezomib Plus Gemcitabine and Carboplatin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer Phase 1
Completed NCT00006929 - Suramin, Paclitaxel, and Carboplatin in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer Phase 2
Completed NCT02879994 - Pembrolizumab in Treating Patients With EGFR Mutant, Tyrosine Kinase Inhibitor Naive Advanced Non-Small Cell Lung Cancer Phase 2
Completed NCT03305380 - Radiomics to Identify Patients at Risk for Developing Pneumonitis, Differentiate Immune Checkpoint Inhibitor-induced Pneumonitis From Other Lung Inflammation and Distinguish Tumour Pseudo-progression From Real Tumour Growth
Completed NCT02728596 - S1415CD, Trial Assessing CSF Prescribing Effectiveness and Risk (TrACER) N/A
Completed NCT02858869 - Pembrolizumab and Stereotactic Radiosurgery for Melanoma or Non-Small Cell Lung Cancer Brain Metastases Phase 1
Completed NCT02897375 - Palbociclib With Cisplatin or Carboplatin in Advanced Solid Tumors Phase 1